Methods for treating anxiety, anxiety disorders and memory impairment using naaladase inhibitors

Abstract

The present invention relates to methods of using NAALADase inhibitors for treating glutamate-mediated diseases, disorders and conditions selected from the group consisting of anxiety, anxiety disorders and memory impairment.

What is claimed is:  
     
       1. A method of treating a glutamate mediated disease, disorder, or condition selected from the group consisting of anxiety, anxiety disorder, and memory impairment in a mammal in need thereof, comprising administering to said mammal an effective amount of a NAALADase inhibitor, wherein said NAALADase inhibitor is a compound of formula II. 
     
     
       2. The method of claim  1 , wherein the NAALADase inhibitor is a compound of formula VI                    
       or a pharmaceutically acceptable equivalent, wherein: 
       n is 0, 1, 2 or 3;  
       Z is SH, SO 3 R 13 , SO 2 R 13 , SOR 13  or S (NR 13 R 14 ) 2 R 15 ; and  
       A is O, S or CR 17 R 18 .  
     
     
       3. The method of claim  2 , wherein Z is SH. 
     
     
       4. The method of claim  3 , wherein R 8  is —(CH 2 ) 2 COOH. 
     
     
       5. The method of claim  3 , wherein the compound of formula VI is selected from the group consisting of: 
       2-(2-sulfanylethyl)pentanedioic acid;  
       3-(2-sulfanylethyl)-1,3,5-pentanetricarboxylic acid;  
       2-(2-sulfanylpropyl)pentanedioic acid;  
       2-(2-sulfanylbutyl)pentanedioic acid;  
       2-(2-sulfanyl-2-phenylethyl)pentanedioic acid;  
       2-(2-sulfanylhexyl)pentanedioic acid;  
       2-(2-sulfanyl-1-methylethyl)pentanedioic acid;  
       2-[1-(sulfanylmethyl)propyl]pentanedioic acid;  
       2-(3-sulfanylpentyl)pentanedioic acid;  
       2-(3-sulfanylpropyl)pentanedioic acid;  
       2-(3-sulfanyl-2-methylpropyl)pentanedioic acid;  
       2-(3-sulfanyl-2-phenylpropyl)pentanedioic acid;  
       2-(3-sulfanylbutyl)pentanedioic acid;  
       2-[3-sulfanyl-2-(phenylmethyl)propyl]pentanedioic acid;  
       2-[2-(sulfanylmethyl)butyl]pentanedioic acid;  
       2-[2-(sulfanylmethyl)pentyl]pentanedioic acid;  
       2-(3-sulfanyl-4-methylpentyl)pentanedioic acid; and  
       pharmaceutically acceptable equivalents.  
     
     
       6. The method of claim  5 , wherein the compound of formula VI is selected from the group consisting of 2-(2-sulfanylethyl)pentanedioic acid, sulfanylpropyl)pentanedioic acid, 2-(3-sulfanylpropyl) pentanedioic acid and pharmaceutically acceptable equivalents. 
     
     
       7. The method of claim  6 , wherein the compound of formula VI is an enantiomer or an enantiomer-enriched mixture. 
     
     
       8. The method of claim  1 , wherein the NAALADase inhibitor is administered in combination with at least one additional therapeutic agent. 
     
     
       9. The method of claim  1 , wherein the glutamate mediated disease, disorder or condition is an anxiety disorder selected from the group consisting of panic attack, agoraphobia, panic disorder, acute stress disorder, chronic stress disorder, specific phobia, simple phobia, social phobia, substance induced anxiety disorder, organic anxiety disorder, obsessive compulsive disorder, post-traumatic stress disorder, generalized anxiety disorder, and anxiety disorder NOS. 
     
     
       10. The method of claim  1 , wherein the glutamate mediated disease, disorder or condition is memory impairment.